Our work is directed towards understanding genetic and developmental factors which affect the functioning of adrenergic neurons. Murine neuroblastoma cells are cultured with and without embryonic heart cells, as a model system for synaptic interactions. We measure changes in tyrosine hydroxylase (EC 1.14.16.2) activity and high affinity uptake of norepinephrine resulting from contacts fromed between neuroblastoma and heart cells. Other aspects of catecholamine metabolism, such as dopamine beta-hydroxylase (EC 1.14.17.1), monoamine oxidase (MAO, EC 1.4.3.4) and catechol 0-methyltransferase (EC 2.1.1.6) activities, are also monitored. In other studies, we have isolated neuroblastoma lines lacking hypoxanthine phosphoribosyl-transferase (HPRT, EC 2.4.2.8) activity as a model system for studying alterations in neuronal functioning associated with the Lesch-Nyhan syndrome in man. Noradrenergic lines lacking HPRT activity show 50-2000 fold reductions in MAO activity, with no other changes in catecholamine metabolism. We are examining the effects of HPRT deficiency on cyclic nucleotide metabolism in an attempt to elucidate the biochemical link between purine and catecholamine metabolism. Three-fold lower levels of MAO activity are also observed in cultured skin fibroblasts from Lesch-Nyhan patients, as compared to controls. We are examining the expression of the A and B forms of MAO in these and other cultured cell lines. BIBLIOGRAPHIC REFERENCES: Giller, E. L., Breakefield, X. O., Christian, C.N., Neale, E. A. and Nelson, P.G.: Expression of neuronal characteristics in culture: Some pros and cons of primary cultures and continuous cell lines. In Golgi Centennial Symposium Proceedings (Ed. M. Santani) Raven Press, New York, pp. 603-623, 1975. Breakefield, X. O., Neale, E. A., Neale, J. H. and Jacobowitz, D. M.: Localized catecholamine storage associated with granules in murine neuroblastoma cells. Brain Res. 92:237-256, 1975.